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Summary Background Preterm birth rates have increased significantly worldwide over the past decade. Few epidemiological studies on the incidence of preterm birth and temporal trends are available in China. This study used national monitoring data from China's National Maternal Near Miss Surveillance System (NMNMSS) to estimate the rate of preterm birth and trends between 2012 and 2018 in China and to assess risk factors associated with preterm birth. Methods In this observational study, data were sourced from the NMNMSS between Jan 1, 2012, and Dec 31, 2018. Pregnancies with at least one livebirth, with the baby born at 28 weeks of gestation or more or 1000 g or more birthweight were included. We estimated the rates of overall preterm, very preterm (born between 28 and 31 weeks’ gestation), moderate preterm (born between 32 and 33 weeks’ gestation), and late preterm (born between 34 and 36 weeks’ gestation) births in singleton and multiple pregnancies and assessed their trends over time. We used logistic regression analysis to examine the associations between preterm birth and sociodemographic characteristics and obstetric complications, considering the sampling strategy and clustering of births within hospitals. Interrupted time series analysis was used to assess the changes in preterm birth rates during the period of the universal two child policy intervention. Findings From Jan 1, 2012, to Dec 31, 2018, 9 645 646 women gave birth to at least one live baby, of whom 665 244 (6·1%) were born preterm. In all pregnancies, the overall preterm birth rate increased from 5·9% in 2012 to 6·4% in 2018 (8·8% increase; annual rate of increase [ARI] 1·3 [95% CI 0·6 to 2·1]). Late preterm births (8·8%; ARI 1·5% [0·9 to 2·2]) and very preterm births (13·3%; ARI 1·8% [0·5 to 3·0]) significantly increased from 2012 to 2018, whereas moderate preterm births did not (3·8%; ARI 0·3% [95% CI –0·9 to 1·5]). In singleton pregnancies, the overall preterm birth rate showed a small but significant 6·4% increase (ARI 1·0% [0·4 to 1·7]) over the 7 year period. In multiple pregnancies, the overall preterm birth rate significantly increased from 46·8% in 2012 to 52·7% in 2018 (12·4% increase; ARI 1·9% [1·2 to 2·6]). Compared with women who gave birth in 2012, those who gave birth in 2018 were more likely to be older (aged ≥35 years; 7·4% in 2012 vs 15·9% in 2018), have multiples (1·6% vs 1·9%), have seven or more antenatal visits (50·2% vs 70·7%), and have antepartum complications and medical disease (17·9% vs 35·1%), but they were less likely to deliver via caesarean section (47·5% vs 45·0%). Compared with the baseline period (January, 2012 to June, 2016), a higher increase in preterm birth was observed after the universal two child policy came into effect in July, 2016 (β=0·034; p=0·03). Interpretation An increase in preterm births was noted for both singleton and multiple pregnancies between 2012 and 2018 in China. China's strategic investment in maternal and neonatal health has been crucial for the prevention of preterm birth. Due to rapid changes in sociodemographic and obstetric factors related to preterm birth—particularly within the context of the universal two child policy—such as advanced maternal age at delivery, maternal complications, and multiple pregnancies, greater efforts to reduce the burden of preterm birth are urgently needed. Funding National Key R&D Program of China, National Health Commission of the People's Republic of China, China Medical Board, WHO, and UNICEF.

Background Tetrahydrobiopterin deficiency (BH4D), a less common form of hyperphenylalaninemia (HPA), can lead to severe developmental retardation if untreated. Little has been reported on the prevalence of BH4D among live births worldwide. This study examined its prevalence across China and between geographical areas within the country. Methods We analyzed data from the Chinese national screening program for HPA in newborns between 2013 and 2019. BH4D prevalence was examined by province, region and the entire country. Provincial-level prevalence was estimated from the number of confirmed BH4D cases and screened newborns, after adjusting for HPA-positive recall rate. Regional- and national-level prevalences were estimated by summing provincial-level prevalences after weighting them by the number of live births. A Poisson distribution was assumed in order to calculate 95% confidence intervals (CIs) for prevalence. Results Among 107,078,115 newborns screened for HPA in China, 380 with BH4D were identified, corresponding to a total prevalence of 3.8 per 1,000,000 live births. Prevalence was higher in eastern regions (5.9 per 1,000,000) and northern regions (4.1 per 1,000,000) of China than in southern regions (1.6 per 1,000,000) or northwestern regions (1.7 per 1,000,000). Across the entire country, 3.9% cases of HPA were diagnosed as BH4D, and this proportion reached as high as 15.1% in the southern part of the country. Conclusions These first insights into BH4D prevalence across China suggest slightly higher prevalence than in other countries, and it varies substantially by region. More attention should be paid to early diagnosis and timely treatment of BH4D.

Patients with lung metastases (LM) from epithelial ovarian cancer (EOC) (EOCLM) usually have a poor prognosis. However, there is no consensus on the optimal management of these patients. In this study, we aimed to take a look at the incidence of LM and factors associated with its occurrence as well as the prognosis in newly diagnosed EOC with LM on a population level. EOC patients diagnosed between the years 2010 and 2016 were identified from the Surveillance, Epidemiology, and End Results (SEER) program database. Multivariable logistic regression and multivariable Cox regression were used to investigate the factors that could predict the occurrence of and prognosis after diagnosis of EOC with LM. Of the 33,418 qualified EOC patients, 2240 (6.7%) were noted to have LMs at the time of EOC diagnosis. Higher T stage, N1 stage, advanced tumor grade, and elevated cancer antigen-125 levels were found to be associated with a higher risk of having LM at the time of EOC diagnosis. The median survival time after diagnosis with EOCLM was found to be 13.0 months (interquartile range: 3.0–34.0 months). Being unmarried and having mucinous histology were both associated with increased all-cause death risk from EOCLM. However, the primary tumor originated from the midline of ovaries, surgical management, and whether patient received chemotherapy or not predicted improved overall survival. The median survival time of patients was significantly longer for EOCLM cases managed surgically (31.0 months) versus those who did not have surgery (4.0 months), as well as EOCLM cases received chemotherapy (23.0 months) versus those who did not have chemotherapy (2.0 months). This retrospective cohort study showed that de novo LM was infrequent in EOC patients overall and when present predicted poor prognosis. The findings can be potentially useful in formulating for follow-up strategies, screening tools, and personalized interventions.

Background The incidence of inborn errors of metabolism varies widely across countries. Very few studies have analyzed the incidence of these disorders in Mainland China. We aimed to estimate the overall and disease-specific incidences of inborn errors of metabolism in Chinese newborns and investigate the geographical distribution of these disorders. Methods A national cross-sectional survey was conducted to investigate newborn inborn errors of metabolism screening by tandem mass spectroscopy in Mainland China between 2016 and 2017. A total of 246 newborn screening centers were surveyed using a standardized questionnaire. We examined the cumulative and disease-specific incidences of inborn errors of metabolism in Mainland China as a whole and in different geographical locations. Results Over 7 million newborns were screened and 2747 were diagnosed with inborn errors of metabolism, yielding an overall incidence of 38.69 per 100,000 births (95% confidence interval: 37.27–40.17). The most common disorders were amino acid disorders (17.14 per 100,000 births, 95% confidence interval: 16.21–18.13), followed by organic acid disorders (12.39 per 100,000 births, 95% confidence interval: 11.60–13.24) and fatty acid oxidation disorders (9.16 per 100,000 births, 95% confidence interval: 8.48–9.89). The overall and disease-specific incidence rates differed significantly across geographical locations (P Conclusions The overall incidence of inborn errors of metabolism in Chinese newborns is relatively high. It is urgent to establish the recommended uniform screening panel for inborn errors of metabolism to guide the national and regional tandem mass spectroscopy newborn screening programs.

Retinoic acid receptor gamma (RARG) belongs to the nuclear receptor superfamily and has 90% homology to RAR alpha (RARA) and RAR beta. The promyelocytic leukemia (PML)-RARA fusion gene has been implicated in acute promyelocytic leukemia (APL). RARG gene rearrangement has been identified in a rare subtype of acute myeloid leukemia (AML) that resembles APL. To date, only 10 cases of gene rearrangements involving RARG (nucleoporin [NUP]98-RARG, promyelocytic leukemia protein-RARG, cleavage and polyadenylation-specific factor 6-RARG, or nucleophosmin [NPM]1-RARG-NPM1) have been reported. These patients show characteristics similar to APL, including bone marrow morphology, coagulation abnormality, and immunophenotype; however, they are resistant to all-trans retinoic acid and arsenic trioxide treatment. Moreover, there is no optimal therapeutic regimen for this subtype of AML. In this study, we report the clinical presentation and experimental findings of a case of AML with NUP98-RARG gene fusion similar to APL and review other cases of RARG gene rearrangement described in the literature.

Objectives Health insurance availability and affordability are vital elements in diagnosis and treatment of patients with cancer and thus constitute clinical significance as well. Although past studies have explored the disparity in mortality figures for patients with different insurance statuses, this population-based study is pioneering in analyzing the changes in cancer mortality risks over time amid macroeconomic shifts. Study design The study uses Surveillance Epidemiology and End Results (SEER) data of 424,889 non-elderly patients with breast, cervical, ovarian, and uterine cancer diagnosed during 2007–2010 and 2011–2015. Methods In addition to discussing incidence figures and insurance patterns, the study uses Kaplan-Meier and Cox's proportional hazard models to examine the changes in survival probability and mortality risks for insurance-stratified patients with female-specific cancer across the two time periods. Results Patients without insurance have an increased risk of mortality over time relative to insured patients. Moreover, uninsured patients face this heightened risk more than Medicaid patients. Discussion Despite public policy measures as well as advancements in diagnostic facilities and treatment technology, the increased relative mortality of patients without insurance limits the long-term affordability of cancer treatment for economically vulnerable patients in comparison with insured patients.

In the early February, 2020, we called up an experts' committee with more than 30 Chinese experts from 11 national medical academic organizations to formulate the first edition of consensus statement on diagnosis, treatment and prevention of coronavirus disease 2019 (COVID-19) in children, which has been published in this journal. With accumulated experiences in the diagnosis and treatment of COVID-19 in children, we have updated the consensus statement and released the second edition recently. The current version in English is a condensed version of the second edition of consensus statement on diagnosis, treatment and prevention of COVID-19 in children. In the current version, diagnosis and treatement criteria have been optimized, and early identification of severe and critical cases is highlighted. The early warning indicators for severe pediatric cases have been summarized which is utmost important for clinical practice. This version of experts consensus will be valuable for better prevention, diagnosis and treatment of COVID-19 in children worldwide.

Untargeted metabolomics based on liquid chromatography-mass spectrometry is affected by nonlinear batch effects, which cover up biological effects, result in nonreproducibility, and are difficult to be calibrate. In this study, we propose a novel deep learning model, called Normalization Autoencoder (NormAE), which is based on nonlinear autoencoders (AEs) and adversarial learning. An additional classifier and ranker are trained to provide adversarial regularization during the training of the AE model, latent representations are extracted by the encoder, and then the decoder reconstructs the data without batch effects. The NormAE method was tested on two real metabolomics data sets. After calibration by NormAE, the quality control samples (QCs) for both data sets gathered most closely in a PCA score plot (average distances decreased from 56.550 and 52.476 to 7.383 and 14.075, respectively) and obtained the highest average correlation coefficients (from 0.873 and 0.907 to 0.997 for both). Additionally, NormAE significantly improved biomarker discovery (median number of differential peaks increased from 322 and 466 to 1140 and 1622, respectively). NormAE was compared with four commonly used batch effect removal methods. The results demonstrated that using NormAE produces the best calibration results.

Objective Ascites, an accumulation of peritoneal fluid, is associated with poor prognosis of certain cancers. The potential mechanism that ascites worsens prognosis has not been well understood. Lipids have been reported to correlate with the prognosis of patients with epithelial ovarian cancer (EOC). Therefore, we aimed here to investigate whether lipids mediate the effect of ascites on the recurrence of EOC. Methods We collected the demographic and pathological data of 437 previously untreated patients with EOC to investigate the influence of ascites on recurrence. To identify the mechanism that mediates the potential influence of ascites on recurrence, we used ultra-performance liquid chromatography coupled with mass spectrometry (UPLC-MS) to determine the plasma lipid profiles of 53 patients with EOC. We used mediation analysis to evaluate if lipids mediated the effects of ascites on the recurrence of EOC. Results Patients with ascites had a poorer prognosis, which was associated with higher levels of carbohydrate antigen-CA125 (CA125) and FIGO stage. We identified six different lipid metabolites that were associated with ascites and recurrence. Mediation analysis revealed that the lipids LysoPC(P-15:0), PC(P-34:4), and PC(38:6) may mediate the effects of ascites on recurrence. Conclusion Our findings suggest that LysoPC(P-15:0), PC(P-34:4), and PC(38:6) mediate the effect of ascites on the prognosis of patients with EOC. We believe therefore that it is reasonable to consider metabolic interventions targeting the metabolism of LysoPC(P-15:0), PC(P-34:4), and PC(38:6) as a palliative treatment for patients with EOC with ascites. Further studies of more patients will be required to validate our findings.

Background As reported, 27-93 % of pregnant women take at least one drug during pregnancy. However, drug exposure during pregnancy still lacks sufficient foetal safety evidence of human origin. It is urgent to fill the knowledge gap about medication safety during pregnancy for optimization of maternal disease treatment and pregnancy drug consultation. Methods and analysis The China Teratology Birth Cohort (CTBC) was established in 2019 and is a hospital-based open-ended prospective cohort study with the aim of assessing drug safety during pregnancy. Pregnant women who set up the pregnancy health records in the first trimester or who seek drug consultation regardless of gestational age in the member hospitals are recruited. Enrolled pregnant women need to be investigated four times, namely, 6–14 and 24–28 weeks of gestational age, before discharge after hospital delivery, and 28–42 days after birth. Maternal medication exposure during pregnancy is the focus of the CTBC. For drugs, information on the type, name, and route of medication; start and end time of medication; single dose; frequency of medication; dosage form; manufacturer; and reason for medication is collected. The adverse pregnancy outcomes collected in the study include birth defects, stillbirth, spontaneous abortion, preterm birth, post-term birth, low birth weight, macrosomia, small for gestational age, large for gestational age and low Apgar score. CTBC uses an electronic questionnaire for data collection and a cloud system for data management. Biological samples are collected if informed consents are obtained. Multi-level logistic regression, mixed-effect negative binomial distribution regression and spline function regression are used to explore the effect of drugs on the occurrence of birth defects. Discussion The findings of the study will assist in further understanding the risk of birth defects and other adverse pregnancy outcomes associated with maternal drug exposure and developing the optimal treatment plans and drug counselling for pregnant women. Trial registration This study was approved by the Research Ethics Committee of the West China Second Hospital of Sichuan University and registered at the Chinese Clinical Trial Registry (http://www.chictr.org.cn/index.aspx, registration number ChiCTR1900022569).

Postterm births are associated with an increased risk of adverse perinatal outcomes, but few studies have investigated the epidemiological characteristics of postterm births. We aimed to estimate the prevalence of postterm births and examine the potential association between maternal sociodemographic and obstetric characteristics and postterm births. Data were collected from China’s National Maternal Near Miss Surveillance System, 2012–2016. A logistic regression was used to assess the association between sociodemographic and obstetric characteristics and postterm births. A Poisson regression was used to determine the crude and adjusted trends of postterm births over time across regions. Among the 6,240,830 singleton births with gestational periods of 37 weeks or longer, 1.16% were postterm. The prevalence of postterm births was significantly higher in the western region and among mothers who delivered at a level ≤2 hospital, had a lower education, or were younger. A reduced risk of postterm births was observed among primiparous women, mothers who previously had a caesarean section, mothers with pregnancy complications, and mothers with ten or more antenatal visits. The risk of postterm births decreased as the number of antenatal visits increased. The overall postterm birth rates significantly decreased from 1.49% in 2012 to 0.70% in 2016. The postterm birth rates were markedly reduced in the east, central, and west regions, and the rate of the decrease was greater in the east than in the west. Furthermore, substantial decreases were observed across regions in 2014 and 2016. In conclusion, multiple sociodemographic and obstetric factors are associated with the prevalence of postterm births. A significant decreasing trend in postterm birth rates was observed in China.

The virtual synchronous generator (VSG) is favored in distributed generation units because it can reduce the rate of change of frequency (ROCOF) in the inverter stand-alone mode. Although the rotor inertia and damping factor can improve the frequency stability of the grid, they deteriorate the transient performance in the grid-connected mode with high current overshoot and power oscillation. The existing solutions improve the transient performance at the cost of larger ROCOF or complex adaptive algorithms, which can sacrifice some frequency stability or lead into potential uncertainties. Aiming at solving this problem effectively, this paper proposes a novel method by adding a pair of pole-zero to the rotor inertia. In this way, the VSG control can not only greatly improve the transient performance in the grid-connected mode, but also the same good ROCOF is maintained for the stand-alone mode. Firstly, the small signal model of VSG control with the improved rotor inertia is derived based on the traditional VSG control. Then the improvement caused by the pole-zero in rotor inertia is analyzed in frequency domain in detail. Finally, the effectiveness of the proposed method is validated by experimental results.

Background Newborn hearing screening (NHS) can reduce the economic and social burden of hearing impairment. To track the progress of the goal set by the National Program of Action for Child Development (NPACD) and to estimate the detection rates of hearing impairment, the present study examined NHS coverage in 2008–2010 and 2016 and the detection of hearing impairment across China in 2016. Methods Licensed medical institutions across China were surveyed in 2012 and 2018 by the National Center for Birth Defects Monitoring of China to collect data for the 2008–2010 period and for 2016 on live births, initial screening rates (total and referral), secondary screening rates (total and referral), and rates of hearing impairment diagnosis among infants who were referred in the secondary screening. To calculate universal newborn hearing screening (UNHS) coverage, the number of newborns who received NHS within 4 weeks after birth was divided by the number of live births. The detection rate of hearing impairment was calculated by combining referral rates on primary and secondary screening with the rate of diagnosis. Results National UNHS coverage increased from 29.9% in 2008 to 86.5% in 2016, with different regions showing different increases. During this period, the number of provinces with UNHS coverage over 90.0% increased from 2 to 17, with UNHS coverage in 2016 being substantially higher in eastern provinces (93.1%) than in western provinces (79.4%). In 2016, the detection rate of hearing impairment across the country was 0.23% (95% CI 0.15–0.25%), and it varied from 0.17% in western provinces to 0.22% in central provinces and 0.28% in eastern provinces. The lowest rate was 0.02% in Heilongjiang Province and the highest rate was 0.63% in Hainan Province. Conclusions National UNHS coverage increased substantially from 2008 to 2016, although provinces and regions still showed differences. The detection rate of infant hearing impairment in China is comparable to that in other countries. A national individual-level information system is urgently needed in China to facilitate the integration of screening, diagnosis and treatment of infant hearing impairment, which may also lead to a more accurate estimate of the detection rate.

Colorectal cancer (CRC) remains an incurable disease. Previous metabolomic studies show that metabolic signatures in plasma distinguish CRC patients from healthy controls. Chronic enteritis (CE) represents a risk factor for CRC, with a 20 fold greater incidence than in healthy individuals. However, no studies have performed metabolomic profiling to investigate CRC biomarkers in CE. Our aims were to identify metabolomic signatures in CRC and CE and to search for blood-derived metabolite biomarkers distinguishing CRC from CE, especially early-stage biomarkers. In this case–control study, 612 subjects were prospectively recruited between May 2015 and May 2016, and including 539 CRC patients (stage I, 102 cases; stage II, 259 cases; stage III, 178 cases) and 73 CE patients. Untargeted metabolomics was performed to identify CRC-related metabolic signatures in CE. Five pathways were significantly enriched based on 153 differential metabolites between CRC and CE. 16 biomarkers were identified for diagnosis of CRC from CE and for guiding CRC staging. The AUC value for CRC diagnosis in the external validation set was 0.85. Good diagnostic performances were also achieved for early-stage CRC (stage I and stage II), with an AUC value of 0.84. The biomarker panel could also stage CRC patients, with an AUC of 0.72 distinguishing stage I from stage II CRC and AUC of 0.74 distinguishing stage II from stage III CRC. The identified metabolic biomarkers exhibit promising properties for CRC monitoring in CE patients and are superior to commonly used clinical biomarkers (CEA and CA19-9).

Background: Breakthroughs have been made in cancer immunotherapy using antibodies against immune checkpoints. But successful immune checkpoint blockade (ICB) responses only occur in a fraction of people, and we have no idea which patients will be the lucky one before treatment. Picking out the effective population accurately can improve the cure rate significantly. We set out to design a novel immunophenotyping approaches for kidney renal clear cell carcinoma (KIRC) based on the tumor immune microenvironment(TIME), which target to distinguish immunotherapy responders. Methods: Five hundred and thirty KIRC samples from The Cancer Genome Atlas (TCGA) were analyzed as the training cohort. Non-negative matrix factorization (NMF) was used to extract immune-related features from complex tumor bulks. We associated the expression patterns with a series of immune-related gene signatures and clinicopathological features. GSE73731 and GSE40435 validation datasets were analyzed to further confirm our findings. Findings: We found that almost 40% of KIRC patients in the training cohort (209/530) were designated as the Immune Class with a high enrichment score for inflammatory response, cytolytic activity, and CD8 T cells (all P

To assess the association between patterns of distant metastases and overall survival in metastatic ovarian cancer and identify prognostic factors for site-specific distant metastases.Data was obtained from the SEER database between 2010 and 2014. Univariate and multivariate Cox proportional hazard models were used to identify variables associated with overall survival. Survival times between different groups were compared using Kaplan-Meier analysis and log-rank tests.We analyzed 1481 patients. The most common distant metastatic site was liver, followed by distant lymph nodes, lung, bone, and brain. The site of distant metastases was an independent prognostic factor for overall survival. Using liver metastases as reference, overall survival was lower for lung metastases (p = 0.0297) and higher for distant lymph node metastases (p = 0.0006). Using distant lymph nodes as reference, distant metastases to the liver (p = 0.0006), lung (p 0.0001), brain (p = 0.0455), and bone (p = 0.0138) were all associated with worse overall survival. The number of metastatic sites did not affect overall survival. We also found that surgery and chemotherapy affected overall survival for patients with distant lymph node metastases only; age, histological subtype, surgery, and chemotherapy affected overall survival for patients with liver metastases only, while histological subtype and chemotherapy affected overall survival for patients with lung metastases only.The site of distant metastases affected overall survival in metastatic ovarian cancer. Patients with specific distant metastatic sites should receive special treatment and management. The identified prognostic factors can help clinician evaluate the prognosis for ovarian cancer patients with distant metastases.

To examine the trends and safety of vaginal birth after caesarean section around the period of the one-child policy relaxation in China.We used data from China's National Maternal Near Miss Surveillance System between 2012 and 2016. To examine trends in vaginal birth after caesarean section, we used Poisson regression with a robust variance estimator. We also assessed the association between vaginal birth after caesarean section and maternal and perinatal outcomes.We analysed 871 636 deliveries by women with a previous caesarean section. Both in 2012 and 2016, the rate of vaginal birth after caesarean section was 9.8%. After adjusting for institutional, sociodemographic and obstetric characteristics, the rate increased by 14% between 2012 and 2016 (adjusted relative risk, aRR: 1.14; 95% confidence interval, CI: 1.07-1.21). Compared to women with a repeat caesarean section, women with a vaginal birth after caesarean section experienced lower incidence of uterine rupture (aRR: 0.26, 95% CI: 0.16-0.42), blood transfusion (aRR: 0.68, 95% CI: 0.53-0.87) and admission to the intensive care unit (aRR: 0.36, 95% CI: 0.25-0.52), but higher incidence of intrapartum stillbirths, (aRR: 7.20, 95% CI: 6.09-8.51), newborns with a 5-minute Apgar score less than 7 (aRR: 1.75, 95% CI: 1.54-1.99) and neonatal death before discharge (aRR: 1.90, 95% CI: 1.61-2.24).Promotion of vaginal birth after caesarean section could increase the rate even further in China. To ensure the safety of mothers and their newborns, national policies and guidelines on vaginal birth after caesarean section are needed.Examiner les tendances et la sûreté de l'accouchement vaginal après une césarienne autour de la période de l'assouplissement de la politique de l'enfant unique en Chine.Nous avons utilisé les données du Système de surveillance national des décès maternels évités de justesse de la Chine entre 2012 et 2016. Afin d'examiner les tendances relatives à l'accouchement vaginal après césarienne, nous avons utilisé une régression de Poisson et un estimateur de variance fiable. Nous avons également évalué le lien entre l'accouchement vaginal après césarienne et les résultats pour la santé maternelle et périnatale.Nous avons analysé 871 636 accouchements de femmes ayant préalablement subi une césarienne. En 2012 et en 2016, le taux d'accouchements vaginaux après césarienne était de 9,8%. Après ajustement en fonction de caractéristiques institutionnelles, sociodémographiques et obstétriques, ce taux a augmenté de 14% entre 2012 et 2016 (risque relatif ajusté, RRa: 1,14; intervalle de confiance, IC, à 95%: 1,07-1,21). Comparées aux femmes ayant subi une césarienne itérative, les femmes accouchant par voie vaginale après une césarienne ont connu une plus faible incidence de rupture utérine (RRa: 0,26; IC à 95%: 0,16-0,42), de transfusion sanguine (RRa: 0,68; IC à 95%: 0,53-0,87) et d'admission dans une unité de soins intensifs (RRa: 0,36; IC à 95%: 0,25-0,52), mais une plus forte incidence de mortinaissances lors de l'accouchement (RRa: 7,20; IC à 95%: 6,09-8,51), de nouveau-nés avec un score d'Apgar à 5 minutes inférieur à 7 (RRa: 1,75; IC à 95%: 1,54-1,99) et de décès néonatals avant la sortie de l'hôpital (RRa: 1,90; IC à 95%: 1,61-2,24).La promotion de l'accouchement vaginal après césarienne pourrait faire progresser davantage encore le taux en Chine. Afin d'assurer la sécurité des mères et de leur nouveau-né, des politiques et des directives nationales sur l'accouchement vaginal après césarienne sont nécessaires.Examinar las tendencias y la seguridad del parto vaginal después de una cesárea durante el periodo de relajación de la política de un solo hijo en China.Se usaron datos del Sistema Nacional de Vigilancia de Casi Accidentes Maternos de China (National Maternal Near Miss Surveillance System) de 2012 a 2016. Para examinar las tendencias del parto vaginal después de una cesárea, se utilizó la regresión de Poisson con un estimador de varianza robusto. También se evaluó la asociación entre el parto vaginal después de una cesárea y los resultados maternos y perinatales.Se analizaron 871 636 partos de mujeres que ya habían pasado por una cesárea. Tanto en 2012 como en 2016, la tasa de partos vaginales después de una cesárea fue del 9,8%. Después de ajustar las características institucionales, sociodemográficas y obstétricas, la tasa aumentó un 14% entre 2012 y 2016 (coeficiente de riesgo ajustado, aRR: 1,14; intervalo de confianza, IC, del 95%: 1,07-1,21). En comparación con las mujeres que repitieron cesárea, las mujeres que tuvieron un parto vaginal después de una cesárea experimentaron una menor incidencia de rotura uterina (aRR: 0,26, IC del 95%: 0,16–0,42), transfusiones de sangre (aRR: 0,68, IC del 95%: 0,53–0,87) y hospitalización en la unidad de cuidados intensivos (aRR: 0,36, IC del 95%: 0,25–0,52), pero una mayor incidencia de mortinatos durante el parto, (aRR: 7,20, IC del 95%: 6,09–8,51), recién nacidos con una puntuación de Apgar de 5 minutos inferior a 7 (aRR: 1,75, IC del 95%: 1,54–1,99) y muerte neonatal antes del alta (aRR: 1,90, IC del 95%: 1,61-2,24).Promover el parto vaginal después de una cesárea podría aumentar aún más la tasa en China. Para garantizar la seguridad de las madres y los recién nacidos, son necesarias políticas y directrices nacionales sobre el parto vaginal después de una cesárea.بحث اتجاهات وسلامة الولادة الطبيعية بعد ولادة قيصرية سابقة خلال فترة سياسة الطفل الواحد في الصين.لقد اعتمدنا على البيانات الواردة من النظام الوطني لمراقبة حالات نجاة الأمهات من الوفاة المؤكدة في الصين خلال الفترة من عام 2012 إلى عام 2016. ولبحث اتجاهات الولادة الطبيعية بعد الولادة القيصرية، فقد قمنا باستخدام تحليل التحوف لبواسون، مع مُقدّر قوي للتباين. كما قمنا أيضا بتقييم الارتباط بين الولادة الطبيعية بعد الولادة القيصرية، والنتائج المترتبة على فترة الأمومة والولادة.قمنا بتحليل 871636 حالة ولادة لسيدات كان لهم تجربة سابقة مع الولادة القيصرية. خلال عامي 2012 و2016، كان معدل الولادة الطبيعية بعد الولادة القيصرية هو 6.8%. وبعد تعديل الخصائص المؤسسية والاجتماعية والديموغرافية والمتعلقة بالولادة، زاد المعدل بنسبة 14% بين عامي 2012 و2016 (نسبة المخاطر المعدلة، aRR: 1.14؛ فاصل الثقة 95%: 1.07–1.21). ومقارنة بالنساء اللاتي خضعن لعملية الولادة القيصرية عدة مرات، فإن النساء اللاتي خضعن للولادة الطبيعية بعد ولادة قيصرية سابقة، شهدن حالات أقل لتمزق الرحم (نسبة المخاطر المعدلة: 0.26، فاصل الثقة 95%: 0.16 إلى 0.42)، ونقل الدم (نسبة المخاطر المعدلة: 0.68، فاصل الثقة 95%: 0.53 إلى 0.87) ودخول وحدة العناية المركزة (نسبة المخاطر المعدلة: 0.36، فاصل الثقة 95%: 0.25 إلى 0.52)، ولكن كان هناك ارتفاع في حالات وفاة الأطفال أثناء الولادة، (نسبة المخاطر المعدلة: 7.20، فاصل الثقة 95%: 6.09 إلى 8.51)، وسجل المواليد الجدد درجة أقل من 7 في فحص Apgar بعد مرور 5 دقائق من الولادة (نسبة المخاطر المعدلة: 1.75، فاصل الثقة 95%: 1.54 إلى 1.99) ووفاة حديثي الولادة قبل الخروج من المستشفى (نسبة المخاطر المعدلة: 1.90، فاصل الثقة 95%: 1.61 إلى 2.24).يمكن أن يؤدي الترويج للولادة الطبيعية بعد الولادة القيصرية إلى زيادة المعدل أكثر من ذلك في الصين. لضمان سلامة الأمهات ومواليدهم، فإن هناك حاجة إلى سياسات وتوجيهات وطنية تنظم الولادة الطبيعية بعد الولادة القيصرية.旨在探讨中国独生子女政策放宽期间，剖腹产术后阴道分娩的趋势和安全性。.我们使用从中国危重孕产妇监测系统中获取的 2012 至 2016 年间的数据。为了检查剖腹产术后阴道分娩的趋势，使用带有稳定方差估计值的 Poisson 回归系统。我们还评估了剖腹产术后阴道分娩与产妇妊娠结局和围产儿结局之间的关系。.我们分析了有剖腹产史的妇女的 871636 次分娩情况。在 2012 和 2016 年，剖腹产术后阴道分娩率均为 9.8％。在调整了机构、社会人口和产科特征后，2012 年至 2016 年期间，剖腹产术后阴道分娩率上升了 14％（调整后的相对风险，aRR：1.14；95% 置信区间，CI：1.07-1.21）。与重复剖腹产妇女相比，剖腹产术后阴道分娩的妇女，子宫破裂（aRR：0.26; 95% CI：0.16-0.42）、输血（aRR：0.68; 95% CI：0.53-0.87）和入住重症监护室（aRR：0.36; 95% CI：0.25-0.52）的发生率较低，但分娩时死胎（aRR：7.20; 95% CI：6.09-8.51）、新生儿 5 分钟 Apgar 评分低于 7 分（aRR：1.75; 95% CI：1.54-1.99）和出院前新生儿死亡（aRR：1.90; 95% CI：1.61-2.24）的发生率较高。.促进剖腹产术后阴道分娩，可以进一步提高中国境内的阴道分娩率。为确保母亲及其新生儿的安全，需要有关剖腹产术后阴道分娩的国家政策和指导方针。.Изучить тенденции и оценить степень безопасности естественных родов после кесарева сечения в период смягчения политики Китая «Одна семья — один ребенок».В период с 2012 по 2016 годы авторы использовали данные Национальной системы надзора за беременными женщинами в Китае. При исследовании тенденций естественных родов после кесарева сечения использовалась регрессия Пуассона с устойчивой оценкой дисперсии. Авторы также оценили связь между естественными родами после кесарева сечения и исходами беременности и родов.Был проанализирован исход 871 636 родов у женщин с предшествующим кесаревым сечением. Как в 2012 году, так и в 2016 году частота естественных родов после кесарева сечения составила 9,8%. После учета поправок на институциональные, социально-демографические и акушерские характеристики показатель увеличился на 14% в период между 2012 и 2016 годами (скорректированный относительный риск, сОР: 1,14; 95%-й доверительный интервал, ДИ: 1,07–1,21). По сравнению с женщинами с повторным кесаревым сечением у женщин с естественными родами после кесарева сечения была более низкая частота возникновения разрыва матки (сОР: 0,26; 95%-й ДИ: 0,16–0,42), необходимости переливания крови (сОР: 0,68; 95%-й ДИ: 0,53–0,87) и перевода в палату реанимации и интенсивной терапии (сОР: 0,36; 95%-й ДИ: 0,25–0,52), но более высокая частота интранатальной смерти плода (сОР: 7,20; 95%-й ДИ: 6,09–8,51), рождения младенцев с оценкой по шкале Апгар менее семи баллов через пять минут после рождения (сОР: 1,75; 95%-й ДИ: 1,54–1,99) и смерти новорожденных до выписки (сОР: 1,90; 95%-й ДИ: 1,61–2,24).Популяризация естественных родов после кесарева сечения может еще больше увеличить эти показатели в Китае. Для обеспечения безопасности матерей и новорожденных необходима национальная политика и рекомендации для практики естественных родов после кесарева сечения.

Previous research suggested an association between maternal exposure to ambient air pollutants and risk of congenital heart defects (CHDs), though the effects of particulate matter ≤10μm in aerodynamic diameter (PM10) on CHDs are inconsistent. We used two machine learning models (i.e., random forest (RF) and gradient boosting (GB)) to investigate the non-linear effects of PM10 exposure during the critical time window, weeks 3-8 in pregnancy, on risk of CHDs. From 2009 through 2012, we carried out a population-based birth cohort study on 39,053 live-born infants in Beijing. RF and GB models were used to calculate odds ratios for CHDs associated with increase in PM10 exposure, adjusting for maternal and perinatal characteristics. Maternal exposure to PM10 was identified as the primary risk factor for CHDs in all machine learning models. We observed a clear non-linear effect of maternal exposure to PM10 on CHDs risk. Compared to 40μgm-3, the following odds ratios resulted: 1) 92μgm-3 [RF: 1.16 (95% CI: 1.06, 1.28); GB: 1.26 (95% CI: 1.17, 1.35)]; 2) 111μgm-3 [RF: 1.04 (95% CI: 0.96, 1.14); GB: 1.04 (95% CI: 0.99, 1.08)]; 3) 124μgm-3 [RF: 1.01 (95% CI: 0.94, 1.10); GB: 0.98 (95% CI: 0.93, 1.02)]; 4) 190μgm-3 [RF: 1.29 (95% CI: 1.14, 1.44); GB: 1.71 (95% CI: 1.04, 2.17)]. Overall, both machine models showed an association between maternal exposure to ambient PM10 and CHDs in Beijing, highlighting the need for non-linear methods to investigate dose-response relationships.

Background:Congenital hypothyroidism (CH) is one of the most frequent, preventable causes of mental retardation. Little has been reported on the epidemiological characteristics of CH in China. We aimed to estimate the incidence of CH in China and investigate its geographical variation.Methods:We analyzed data from the nationwide newborn screening program for CH between 2013 and 2015. Poisson regression was used to generate the odds ratios (ORs) and 95% confidence intervals (CIs) between the rates of CH and selected demographic characteristics and assess the potential association between CH incidence and geographical locations.Results:A total of 18,666 patients with CH were identified from 45.2 million newborns, yielding an overall incidence rate of 4.13 per 10,000 live births. Compared with those in the remote area, regardless of infant sex, a higher incidence risk for CH was present in newborns in coastal areas and inland areas (females: OR=2.00, 95% CI: 1.86–2.16 and OR=1.74, 95% CI: 1.61–1.87, respectively; males: OR=1.70, 95% CI: 1.59–1.83 and OR=1.52, 95% CI: 1.42–1.63, respectively). Additionally, the highest risk of CH for thyroid-stimulating hormone (TSH) screening values Conclusions:The overall incidence of CH is high in China. The significant geographical variations of CH incidence are presented in this study.

With the continuous development of industrial technology, the weak current plays an increasingly important role in all fields of life. In order to facilitate the user to carry, the study of contactless weak current measurement technology is also emerging. This article’s design idea is based on two-dimensional reluctance sensor device built non-contact weak current detection system. The system uses the reluctance sensor HMC1002 to collect the current signal and the temperature sensor DS18B20 to compensate the temperature. The signals collected by the reluctance sensor and the temperature sensor are extremely weak. After being amplified by the amplifying circuit, the signal is conducive to subsequent detection and processing. Filter circuit can filter out interference signals to achieve the goal of improving accuracy. After the corresponding algorithm of the microcontroller will convert the signal voltage, easy to read and store, thus designing a non-contact current measurement capable of detecting weak currents and achieving higher accuracy.

Background Little is known about the epidemiology of congenital hydrocephalus (CH) in China. This study aimed to depict recent changes in CH prevalence and perinatal outcomes of the affected newborns. Methods Data were obtained from the Chinese Birth Defects Monitoring Network (CBDMN), which collects demographic information on all newborns above 28 weeks of gestation, and clinical information on neonates with congenital anomalies. CH cases delivered during 2005–2012 were analyzed. Poisson regression was used to calculate prevalence ratios (PR) and 95% confidence intervals, and linear chi-square test was used to examine time trend of CH prevalence. Results Five thousand two hundred forty-five isolated and 1245 associated CH cases were identified among 10,574,061 newborns, yielding the prevalence of 4.96, 1.18 and 6.14 per 10,000 births for the isolated, associated and overall hydrocephalus, respectively. The annual prevalence of CH presented a decreasing trend (from 7.52 to 5.98 per 10,000 births, P

// Fan Zhang 1 , Yuanyuan Zhang 1 , Weiwei Zhao 1 , Kui Deng 1 , Zhuozhong Wang 1 , Chunyan Yang 1 , Libing Ma 1 , Margarita S. Openkova 2 , Yan Hou 1 and Kang Li 1 1 Department of Epidemiology and Biostatistics, School of Public Health, Harbin Medical University, Harbin, P.R. China 2 Harbin Medical University, Harbin, P.R. China Correspondence to: Yan Hou, email: // Kang Li, email: // Keywords : systematic review; metabolomics; CRC; biomarkers; pathway Received : October 31, 2016 Accepted : February 06, 2017 Published : March 30, 2017 Abstract Colorectal cancer (CRC) remains an incurable disease. There are no effective noninvasive techniques that have achieved colorectal cancer (CRC) diagnosis, prognosis, survival and recurrence in clinic. To investigate colorectal cancer metabolism, we perform an electronic literature search, from 1998 to January 2016, for studies evaluating the metabolomic profile of patients with CRC regarding the diagnosis, recurrence, prognosis/survival, and systematically review the twenty-three literatures included. QUADOMICS tool was used to assess the quality of them. We highlighted the metabolism perturbations based on metabolites and pathway. Metabolites related to cellular respiration, carbohydrate, lipid, protein and nucleotide metabolism were significantly altered in CRC. Altered metabolites were also related to prognosis, survival and recurrence of CRC. This review could represent the most comprehensive information and summary about CRC metabolism to date. It certificates that metabolomics had great potential on both discovering clinical biomarkers and elucidating previously unknown mechanisms of CRC pathogenesis.

Based on the characteristics of wireless communication technology and Wireless Sensor Network, this paper studies the well site environmental monitoring system. The relevant hardware and software of the system are designed to monitor the well site environment, thus preventing downhole accidents. The system uses the wireless ZigBee technology as the transmission mode, and combines the virtual instrument technology to design the upper machine interface. The test results show that the system can monitor the outdoor environment in real time. When the environmental parameters exceed the set value, the corresponding location of the LabVIEW interface will send an alarm.

Background: Primary Epithelial Ovarian Cancer (EOC), a malignant gynecologic disease, is considered one of the leading causes of mortality in women. The development of Liver Metastases (LM) in women with primary ovarian cancer commonly results in a poorer prognosis. This retrospective population-based study aims to measure the prevalence, prognostic factors, and associated risk factors for epithelial ovarian cancer patients with liver metastases (EOCLM). Materials and Methods: The current study cohort of patients based on the Surveillance, Epidemiology, and End Results (SEER) database identified with primary ovarian cancer between the years 2010 and 2016. A chi-square test was employed to compare Metastatic differences among demographic and clinical factors. Univariable and multivariable logistic regression analysis models were used to predict related prognostic factors for LM development. 7-year Kaplan-Meier curves were applied to compare the survival patterns of patients with and without LM. The Multivariable Cox regression model was used to estimate potential risk factors associated with LM related deaths. Results: 33895 eligible primary EOC patients were identified. Among them 2635 (7.77%) patients were initially diagnosed with de novo LM, and 31260 (92.23%) without metastases disease to any site. Non-serous histology type; Malignant Brenner Carcinoma, NOS (OR 1.94; CI: 1.39-2.71; P

Objective Cancer patients exhibit disparity in mortality risks across demographic divisions as well as insurance groups. The effects of macroeconomic environment also vary for such strata. This study analyses the gaps between mortality risks for male and female cancer patients with and without insurance and examines how such gaps transform over time with macroeconomic shifts. Methods Demographic, clinical and treatment records of 45,750 melanoma and 91,157 lung cancer patients diagnosed in 2007-2009 and 2011-2013 were extracted from Surveillance, Epidemiology and End Results (SEER) database. Kaplan-Meier test was applied to ascertain survival probability of each insurance group, while Cox proportional hazard model was used to assess relative mortality risk for Medicaid and uninsured patients, for the whole data as well as separately for both time periods and genders. Results Both the hazard ratios and change thereof over time are greater for female patients without insurance, than for male patients. More than any insurance-gender subgroup, uninsured female patients of melanoma have much increased hazard ratios, from 1.41 [95% confidence interval (CI), 1.04-1.92] to 2.22 [95% CI, 1.67-2.94]. Conclusion Despite diagnostic improvements and technology advancements, the adverse effects of macroeconomic crisis are associated with increased relative mortality risks for cancer patients without insurance, more for women than men.

ObjectiveTo describe the epidemiology of holoprosencephaly (HPE) in China with special reference to prevalence and associated anomalies.MethodsData were abstracted from the Chinese Birth Defects Monitoring Network for the period 2007-2014. Birth prevalence of HPE were assessed by birth year, fetal/infant sex, maternal age, and maternal residential area. Poisson regressions were used to calculate the crude and adjusted prevalence ratios (PR) and their 95% confidence intervals, and linear chi-square test was used to explore time trend for the prevalence of HPE.ResultsA total of 1222 HPE cases were identified in 13,284,142 births, yielding an overall prevalence of 0.92 per 10,000 births. The annual prevalence of HPE presented an upward trend (PConclusionsHPE is an important perinatal health issue because of its poor prognosis. This is the first study depicting a picture of epidemiological characteristics of HPE in China, which can provide useful references for future studies.

Pneumoconiosis is one of the most serious occupational diseases in China, which seriously endangers the health of most workers in dust environments. The diagnosis of pneumoconiosis is very complex and cumbersome, which relies mostly on doctor’s medical knowledge and clinical reading experiences of X-ray chest film. Traditional image processing approach has helped doctors to reduce the misdiagnosis but with lower accuracy. An improved CNN-based pneumoconiosis diagnosis method on X-ray chest films is proposed to predict pneumoconiosis disease. The CNN structure is decomposed from \(5\times 5\) convolution kernel into two \(3\times 3\) convolution kernels to optimize the execution. Compared with GoogLeNet, the proposed GoogLeNet-CF achieves higher accuracy and gives a good result in the diagnosis of pneumoconiosis disease.

The USB universal serial bus is widely used in host computer control and data information transmission due to its plug-and-play, hot-swap support, and flexible use. However, due to cable loss and USB protocol restrictions, high-speed USB signals can only support a transmission distance of 5 meters. In this paper, there shows an engineering application design of the signal transmission scheme based on the USB signal processing chip CH317. Convert hi-speed USB signal into optical Ethernet signal to achieve long-distance transmission of high-speed USB signals. Since there is no test standard at the application layer for hi-speed USB signal, in this paper design a complete test scheme for this transmission method at the hardware layer and application layer according to the existing test standards of hi-speed USB signal and Ethernet. It has certain reference significance for the application of hi-speed USB signal long-distance transmission in engineering.

Poor graft function (PGF) is a fatal complication following allogeneic haematopoietic stem cell transplantation. However, the underlying mechanism is unclear. Effective cross-talk between haematopoietic stem cells (HSCs) and bone marrow microenvironment is important for normal haematopoiesis. Normal HSCs reside in a hypoxic bone marrow microenvironment that protects them from oxidative stress that would otherwise inhibit their self-renewal and results in bone marrow failure. Whether an increased level of reactive oxygen species (ROS) causes PGF following allotransplant is unclear. Using a prospective case-pair study, we identified increased levels of ROS in CD34+ bone marrow cells in subjects with PGF. Elevated ROS levels was associated with an increased frequency of DNA strand breaks, apoptosis, exhaustion of quiescent CD34+ cells and defective colony-forming unit plating efficiency, particularly in the CD34+CD38- fraction. Up-regulated intracellular p53, p21, caspase-3 and caspase-9 levels (but not p38) were detected in CD34+ cells, particularly in the CD34+CD38- fraction. To further study the potential role of ROS levels in post-transplant haematopoiesis, CD34+ bone marrow cells from subjects with good graft function were treated with H2O2. This increased ROS levels resulting in defective CD34+ cells, an effect partially reversed by N-acetyl-L-cysteine. Moreover, CD34+ bone marrow cells from the donors to subjects with poor or good graft function exhibited comparable haematopoietic reconstitution capacities in the xeno-transplanted NOD-PrkdcscidIL2rgnull mice. Thus, even if the transplanted donors' bone marrow CD34+ cells are functionally normal pre-transplant, ROS-induced apoptosis may contribute to the exhaustion of CD34+ bone marrow cells in subjects with PGF following allotransplant.

BACKGROUND Prostate cancer is a heterogeneous malignancy with outcome difficult to predict. Currently, there is an urgent need to identify novel biomarkers that can accurately predict patient outcome and improve the treatment strategy. The aim of this study was to investigate the methylation status of PCDH10 in serum of prostate cancer patients and its potential relevance to clinicopathological features and prognosis. MATERIAL AND METHODS The methylation status of PCDH10 in serum of 171 primary prostate cancer patients and 65 controls was evaluated by methylation-specific PCR (MSP), after which the relationship between PCDH10 methylation and clinicopathologic features was evaluated. Kaplan-Meier survival analysis and Cox analysis were used to evaluate the correlation between PCDH10 methylation and prognosis. RESULTS PCDH10 methylation occurred frequently in serum of prostate cancer patients. Moreover, PCDH10 methylation was significantly associated with higher preoperative PSA level, advanced clinical stage, higher Gleason score, lymph node metastasis, and biochemical recurrence (BCR). In addition, patients with methylated PCDH10 had shorter BCR-free survival and overall survival than patients with unmethylated PCDH10. Univariate and multivariate Cox proportional hazards model analysis indicated that PCDH10 methylation in serum is an independent predictor of worse BCR-free survival and overall survival. CONCLUSIONS PCDH10 methylation in serum is a potential prognostic biomarker for prostate cancer.

Renal clear cell carcinoma (RCC) patients who do not achieve optimal control of progression with immune checkpoint blockade (ICB) should be further studied. Unsupervised consensus clustering was used to group 525 RCC patients based on two typical ICB pathways, CTLA-4 and pogrammed death 1 (PD-1)/programmed death-ligand 1 (PD-L1), as well as two new discovered regulators, CMTM6 and CMTM4. Three immune molecular subtypes (IMMSs) with different clinical and immunological characteristics were identified (type I, II, and III), among which there were more stage I and low-grade tumors in type I RCC than in type II and III. The proportion of males was highest in type II RCC. Overall survival of type II and III was similar (5.2 and 6 years) and statistically shorter than that of type I (7.6 years) before and after adjusting for age and gender. When conducting stratified analysis, our IMMSs were able to identify high-risk patients among middle-aged patients, males, and stage IV patients. Among the differentially expressed genes, approximately 84% were highly expressed in type II and III RCC. Genes related to ICB (CTLA-4, CD274, and PDCD1LG2) and cytotoxic lymphocytes (CD8A, GZMA, and PRF1) were all highly expressed in type II and III RCC. These results documented that patients with type II and III cancer may be more sensitive to anti-CTLA-4 therapy, anti-PD-1/PD-L1 therapy, and a combination of immunotherapies. High expression of CMTM4 in type I RCC (69%) and a statistically significant interaction of CD274 and CMTM6 indicated that CMTM4/6 might be new therapy targets for type I, who are resistant to ICB.

Colorectal cancer (CRC) is a clinically heterogeneous disease, which necessitates a variety of treatments and leads to different outcomes. Only some CRC patients will benefit from neoadjuvant chemotherapy (NACT). An accurate prediction of response to NACT in CRC patients would greatly facilitate optimal personalized management, which could improve their long-term survival and clinical outcomes. In this study, plasma metabolite profiling was performed to identify potential biomarker candidates that can predict response to NACT for CRC. Metabolic profiles of plasma from non-response (n = 30) and response (n = 27) patients to NACT were studied using UHPLC–quadruple time-of-flight)/mass spectrometry analyses and statistical analysis methods. The concentrations of nine metabolites were significantly different when comparing response to NACT. The area under the receiver operating characteristic curve value of the potential biomarkers was up to 0.83 discriminating the non-response and response group to NACT, superior to the clinical parameters (carcinoembryonic antigen and carbohydrate antigen 199). These results show promise for larger studies that could result in more personalized treatment protocols for CRC patients.

Objective To examine how the relaxation of the one child policy and policies to reduce caesarean section rates might have affected trends over time in caesarean section rates and perinatal and pregnancy related mortality in China. Design Observational study. Setting China’s National Maternal Near Miss Surveillance System (NMNMSS). Participants 6 838 582 births at 28 completed weeks or more of gestation or birth weight ≥1000 g in 438 hospitals in the NMNMSS between 2012 and 2016. Main outcome measures Obstetric risk was defined using a modified Robson classification. The main outcome measures were changes in parity and age distributions and relative frequency of each Robson group, crude and adjusted trends over time in caesarean section rates within each risk category (using Poisson regression with a robust variance estimator), and trends in perinatal and pregnancy related mortality over time. Results Caesarean section rates declined steadily between 2012 and 2016 (crude relative risk 0.91, 95% confidence interval 0.89 to 0.93), reaching an overall hospital based rate of 41.1% in 2016. The relaxation of the one child policy was associated with an increase in the proportion of multiparous births (from 34.1% in 2012 to 46.7% in 2016), and births in women with a uterine scar nearly doubled (from 9.8% to 17.7% of all births). Taking account of these changes, the decline in caesarean sections was amplified over time (adjusted relative risk 0.82, 95% confidence interval 0.81 to 0.84). Caesarean sections declined noticeably in nulliparous women (0.75, 0.73 to 0.77) but also declined in multiparous women without a uterine scar (0.65, 0.62 to 0.77). The decrease in caesarean section rates was most pronounced in hospitals with the highest rates in 2012, consistent with the government’s policy of targeting hospitals with the highest rates. Perinatal mortality declined from 10.1 to 7.2 per 1000 births over the same period (0.87, 0.83 to 0.91), and there was no change in pregnancy related mortality over time. Conclusions China is the only country that has succeeded in reverting the rising trends in caesarean sections. China’s success is remarkable given that the changes in obstetric risk associated with the relaxation of the one child policy would have led to an increase in the need for caesarean sections. China’s experience suggests that change is possible when strategies are comprehensive and deal with the system level factors that underpin overuse as well as the various incentives at work during a clinical encounter.

Background Many studies have demonstrated that right-sided colon cancer (RCC) has a higher mortality rate and worse prognosis than left-sided colon cancer (LCC). However, the underlying biological mechanism that can account for these differences is unclear. Methods In this study, plasma metabolic profiles in 147 LCC patients and 105 RCC patients were systematically analyzed by the ultra high performance liquid chromatography quadruple time-of-flight mass spectrometry (UHPLC-QTOF/MS) platform in conjunction with univariate and multivariate statistical analysis. Results Metabolic signatures revealed considerable differences between patients with RCC and LCC, and clear separations were observed between the two groups in partial least-squares discriminant analysis score plots. In total, six metabolites were identified as potential metabolite markers for tumor location in RCC compared with LCC, including upregulated trimethylamine N-oxide and indoxyl sulfate, and downregulated anserine, L-targinine, gamma-glutamyl-gamma-aminobutyraldehyde and pyridoxal 5′-phosphate. These differences highlight that significant alternations occur in the pathways of methane metabolism, arginine and proline metabolism, histidine metabolism, beta-alanine metabolism and vitamin B6 metabolism in RCC compared with LCC. Conclusions Identified biomarkers and metabolic pathways may facilate our understanding of the different mortality rates and prognoses between RCC and LCC.

BACKGROUND Previous studies have shown an inconsistent time trend on the prevalence of anotia and microtia. Little has been reported on the epidemiologic characteristics of anotia and microtia in the Chinese population. METHODS Data from 1996-2007 were obtained from the Chinese Birth Defects Monitoring Network in China. Birth prevalence of anotia and microtia were assessed according to demographic characteristics and annual time trend. Poisson regression was used to calculate crude and adjusted prevalence ratios (APRs) and 95% confidence intervals (CIs) for selected demographic characteristics and subgroups of anotia and microtia. RESULTS A total of 1933 cases with anotia/microtia were identified among 6,308,594 live births, stillbirths, and terminations of pregnancy, yielding a rate of 3.06 per 10,000 births. Isolated anotia/microtia had a prevalence of 2.25 per 10,000 births, whereas among nonisolated cases, the prevalence was 0.81 per 10,000 births. The prevalence rates of anotia/microtia increased significantly during 1996-2007 (p

Serous ovarian cancer (SOC) is the most common form of the histological subtype of epithelial ovarian cancer, with the worst clinical outcome. Despite improvements in surgery and chemotherapy, most patients with SOC experience recurrence within 12-18 months of first-line treatment. Current studies are unable to robustly predict the recurrence of SOC, and more accurate predictive models are urgently required. We have, therefore, developed a novel pathway-structured model to predict the recurrence of SOC. We trained the model on a set of 333 patients and validated it in 3 diversified validation datasets of 403 patients. Genes significantly associated with recurrence within each pathway were identified using a Cox proportional hazards model based on LASSO estimation in the training dataset. Next, a pathway-structured scoring matrix was obtained after computation of the prognostic score for each pathway by fitting to the Cox proportional hazards model. With the pathway-structure scoring matrix as an input, the pathway-based recurrent signatures were identified using the Cox proportional hazards model based on LASSO estimation and the significant pathway-based signatures were externally validated in 3 independent datasets. Meanwhile, our pathway-structured model was compared with a commonly used gene-based model. Our results revealed that our 12 pathway-based signatures successfully predicted the recurrence of SOC with high accuracy in the training dataset and in the 3 validation datasets. Moreover, our pathway-structured model was superior to the gene-based model in 4 datasets. The pathways selected in our study will provide new insights into the pathogenesis and clinical treatments of SOC.

High-grade serous ovarian cancer (HGSC) is an aggressive cancer with a worse clinical outcome. Therefore, studies about the prognosis of HGSC may provide therapeutic avenues to improve patient outcomes. Since genome alteration are manifested at the protein level, we integrated protein and mRNA data of ovarian cancer from The Cancer Genome Atlas (TCGA) and Clinical Proteomic Tumor Analysis Consortium (CPTAC) and utilized the sparse overlapping group lasso (SOGL) method, a new mechanism-driven variable selection method, to select dysregulated pathways and crucial proteins related to the survival of HGSC. We found that biosynthesis of amino acids was the main biological pathway with the best predictive performance (AUC = 0.900). A panel of three proteins, namely EIF2B1, PRPS1L1 and MAPK13 were selected as potential predictive proteins and the risk score consisting of these three proteins has predictive performance for overall survival (OS) and progression free survival (PFS), with AUC of 0.976 and 0.932, respectively. Our study provides additional information for further mechanism and therapeutic avenues to improve patient outcomes in clinical practice.

Previous metabolomic studies have revealed that plasma metabolic signatures may predict epithelial ovarian cancer (EOC) recurrence. However, few studies have performed metabolic profiling of pre- and post-operative specimens to investigate EOC prognostic biomarkers. The aims of our study were to compare the predictive performance of pre- and post-operative specimens and to create a better model for recurrence by combining biomarkers from both metabolic signatures. Thirty-five paired plasma samples were collected from 35 EOC patients before and after surgery. The patients were followed-up until December, 2016 to obtain recurrence information. Metabolomics using rapid resolution liquid chromatography–mass spectrometry was performed to identify metabolic signatures related to EOC recurrence. The support vector machine model was employed to predict EOC recurrence using identified biomarkers. Global metabolomic profiles distinguished recurrent from non-recurrent EOC using both pre- and post-operative plasma. Ten common significant biomarkers, hydroxyphenyllactic acid, uric acid, creatinine, lysine, 3-(3,5-diiodo-4-hydroxyphenyl) lactate, phosphohydroxypyruvic acid, carnitine, coproporphyrinogen, l-beta-aspartyl-l-glutamic acid and 24,25-hydroxyvitamin D3, were identified as predictive biomarkers for EOC recurrence. The area under the receiver operating characteristic (AUC) values in pre- and post-operative plasma were 0.815 and 0.909, respectively; the AUC value after combining the two sets reached 0.964. Plasma metabolomic analysis could be used to predict EOC recurrence. While post-operative biomarkers have a predictive advantage over pre-operative biomarkers, combining pre- and post-operative biomarkers showed the best predictive performance and has great potential for predicting recurrent EOC.

The purpose of this paper is to propose a design of an automobile driver-assistance system. It uses the STC12C5A60S2 as its main controller, and the HC-SR04 as its ultrasonic ranging. Then, the sensor DHT11 is responsible for the external temperature and humidity measurement as well as the velocity correction. These help to improve the precision of the ultrasonic measurement. Through the combination of the vehicle distance detecting and the photo resistance monitoring the external illuminance, we can realize the vehicle-headlights intelligent switching. LCD12864 is an information display combining all the information such as temperature, humidity, vehicle distance and so on, and finally conduct the collision warning via the buzzer. The experimental results show that the system designed has advantages of reliable operation, simple structure, low price and double functions as the collision warning and the vehicle-headlights intelligent switching, which ensures it a good application prospect.

To introduce the National Maternal Near Miss Surveillance System (NMNMSS) in detail and to report the composition of maternal near miss (MNM) in China. The NMNMSS was established by the National Health Commission at the end of 2010, covered over 400 health facilities from 30 provinces in China. The NMNMSS was designed to collect individual information for every pregnant woman admitted to obstetric department in the sampled health facilities. Cross tabulations and correlations were used to describe the distribution of population and sampled facilities in the NMNMSS, and to calculate the MNM mortality ratio for different complications and organ dysfunctions. The individual survey forms of 9,051,638 pregnant women were collected in the NMNMSS between 2012 and 2017. Compared with urban areas, there are very few well-quality medical resources in rural areas. Most women with pregnancy complications in rural areas can only be treated in Level 2 and lower hospitals. MNM in women with indirect obstetric complications received treatment more frequently in Level 3 hospital. The most common maternal complications in severe maternal outcomes (including maternal near miss and maternal death) are obstetrics hemorrhage (58.7%), hypertension disorder (28.0%), and severe anemia (20.6%). The overall MNM mortality ratio is 38:1. The MNM mortality ratios are lowest in amniotic fluid embolism, HIV/AIDS, heart disease, thrombophlebitis, and sepsis. For different organ dysfunctions, the ranks of the MNM mortality ratio from low to high are renal dysfunction, respiratory dysfunction, cardiovascular dysfunction, hepatic dysfunction, neurologic dysfunction, uterine dysfunction, coagulation dysfunction. The NMNMSS is a well-established hospital-based surveillance system for maternal complications in China. It can identify the maternal complications that need to improve health care immediately in China through a powerful longitudinal real-world evidence.

ObjectiveThis study examines the incidence and spatial clustering of phenylketonuria (PKU) in China between 2013 and 2017.MethodsData from the Chinese Newborn Screening Information System were analysed to assess PKU incidence with 95% CIs by province, region and disease severity. Spatial clustering of PKU cases was analysed using global and local spatial autocorrelation analysis in the geographic information system.ResultsThe database contained 4925 neonates with confirmed PKU during the study period, corresponding to an incidence of 6.28 (95% CI: 6.11 to 6.46) per 100 000 neonates screened. Incidence was highest in the provinces of Gansu, Ningxia and Qinghai, where it ranged from 19.00 to 28.63 per 100 000 neonates screened. Overall incidence was higher in the northern part of the country, where classical disease predominated, than in the southern part, where mild disease predominated. PKU cases clustered spatially (global Moran’s I=0.3603,Z=5.3097, pConclusionsChina shows an intermediate PKU incidence among countries, and incidence differs substantially among Chinese provinces and between northern and southern regions. Our results suggest the need to focus efforts on screening, diagnosing and treating PKU in high-incidence provinces.

ObjectiveUntil now, little was known about the epidemiological characteristics of twins in China due to a lack of reliable national data. In this study, we aimed to analyze temporal trends and perinatal mortality of twins from China.MethodsData on twins between 2007 and 2014 were obtained from the China National Population-Based Birth Defects Surveillance System. Twin and singleton deliveries after at least 28 weeks of gestation were recruited and followed until postnatal day 42. Twinning rates were defined as the number of twin individuals per 1000 births(stillbirths and live births). The Weinberg's differential method was utilized to estimate the number of monozygotic and dizygotic twins.ResultsDuring 2007-2014, the twinning rate increased by 32.3% from 16.4 to 21.7 per 1000 total births with an average of 18.8‰. Among twins, both the perinatal mortality rate (26.1 per 1000 total births) and neonatal death rate (15.7 per 1000 live births) presented a downward tendency but remained at a high level. Large urban-rural and geographic disparities were identified in twinning rates, in perinatal and neonatal mortality, and in their temporal trends.ConclusionsThe upward trend of twinning rates in China paired with the relatively high rates of perinatal and neonatal mortality among twins highlights the need for improved perinatal care in the light of socio-demographic differences.

Objective This study aims to evaluate the association between folic acid (FA) supplementation and congenital heart defects (CHDs). Methods This hospital-based case–control study initiated in 2010 in China analyzed 358 cases and 422 controls. The adjusted odds ratio (AOR) calculated using a logistic model was used to assess the association between FA supplementation and CHDs. Results Compared with a mother who reported no FA supplementation, mothers who reported FA supplementation were less likely to have offspring with isolated CHD(s) (AOR = 0.52, 0.34–0.78) and multiple complex conditions (AOR = 0.27, 0.14–0.55). However, mothers who reported FA supplementation for less than 1 month regardless of the start time of supplementation, did not have a significantly lower risk of having an offspring with isolated or multiple complex conditions. Mothers who reported FA supplementation for ≧ 3 months beginning before conception had a significantly lower risk of having children with isolated CHD(s) (AOR = 0.31, 0.18–0.54). Conclusion FA-supplementation is associated with reduced risk of CHDs. The earlier FA supplementation begins before pregnancy and the longer supplementation lasts, the lower the risk of CHDs is.

Background Maternal smoking during pregnancy has been consistently associated with an increased risk of congenital heart defects (CHDs). However, few studies have reported the association between paternal smoking during pregnancy and CHDs among offspring. This report presents the first case-control study to investigate the possible association between periconceptional paternal smoking and CHDs in China. Methods From February 2010 through October 2011, 284 case fetuses with nonsyndromic CHDs and 422 control fetuses with no birth defects were recruited. The mothers of cases and controls were interviewed regarding whether the fathers of fetuses smoked and avoided the mothers while smoking during the periconceptional period. An unconditional logistic regression was used to calculate the adjusted odds ratios (AORs) and 95% confidence intervals (CIs) while controlling for potential confounders. RESULTS Light paternal smoking increased the risk of isolated conotruncal heart defects (AOR, 2.23; 95% CI, 1.05, 4.73). Medium paternal smoking seemed to be associated with septal defects (AOR, 2.04; 95% CI, 1.05, 3.98) and left ventricular outflow tract obstructions (AOR, 2.48; 95% CI, 1.04, 5.95). Heavy paternal smoking was also associated with isolated conotruncal heart defects (AOR, 8.16; 95% CI, 1.13, 58.84) and left ventricular outflow tract obstructions (AOR, 13.12; 95% CI, 2.55, 67.39). Paternal smoking with no avoidance behavior was associated with an increased risk of these CHDs subtypes. CONCLUSIONS Periconceptional paternal smoking increased the risk of isolated conotruncal heart defects, septal defects and left ventricular outflow tract obstructions. The avoidance behavior of paternal smokers may decrease the risk of selected CHDs. Birth Defects Research (Part A) 97:210–216, 2013. © 2013 Wiley Periodicals, Inc.

Autism spectrum disorders are a member of the pervasive developmental disorders (PDDs) that have been increasing dramatically since described by Leo Kanner in 1943. In the past decade, the number of epidemiological publications addressing air pollution exposures and autism has grown correspondingly, but the association is still unclear. Whether air pollutants play a causal role and which substances are related with autism requires further study. We systematically reviewed the literature from 2005 to 2016 in MEDLINE (National Library of Medicine), Web of Science, and PubMed and summarized the association between different air pollutants and autism. Furthermore, we further discussed the exposure time window and potential confounders that should be considered in the association analysis studies. Our objective is to summarize the association between different air pollutants and autism with literature, which has been published since 2005, and explore whether the exposure time window and potential confounders have influence on this association. These results could provide more comprehensive information about the association between air pollutants and autism and be helpful towards further validation study. Graphical abstract ᅟ.

Rationale:Pertussis has re-emerged on a global scale and is an ongoing public health problem, even in countries with high rates of vaccination. Hyperleukocytosis [white blood cell (WBC) count >100 × 109/L] is a rare complication that strongly predicts mortality in cases of severe pertussis.P

In the indoor, wireless location system based on time difference of arrival(TDOA) has poor anti-interference ability, in the system, especially the non-line-of-sight is the largest interference which causes position's results serious distortion. An algorithm for identification of non-line-of-sight is presented to improve the anti-interference ability of the location system, the non-line-of-sight is identified and discarded by two measurements' comparison and measurements analysis between each base station and mobile station, it enhances the anti-interference ability and stability of the system.

BACKGROUND Prostate cancer is a one of the most common malignant diseases in men worldwide. Now it is a challenge to identify patients at higher risk for relapse and progression after surgery, and more novel prognostic biomarkers are needed. The aim of this study was to investigate the clinical significance of protocadherin17 (PCDH17) methylation in serum and its predictive value for biochemical recurrence (BCR) after radical prostatectomy. MATERIAL AND METHODS We evaluated the methylation status of PCDH17 in serum samples of 167 early-stage prostate cancer patients and 44 patients with benign prostatic hyperplasia (BPH) using methylation-specific PCR (MSP), and then evaluated the relationship between PCDH17 methylation and clinicopathologic features. Kaplan-Meier survival analysis and Cox analysis were used to evaluate its predictive value for BCR. RESULTS The ratio of PCDH17 methylation in prostate cancer patients was higher than in patients with BPH. Moreover, PCDH17 methylation was significantly associated with advanced pathological stage, higher Gleason score, higher preoperative PSA levels, and BCR. Kaplan-Meier survival analysis indicated that patients with methylated PCDH17 had shorter BCR-free survival time compared to patients with unmethylated PCDH17. Cox regression analysis indicated that PCDH17 methylation was an independent predictive factor for the BCR of patients after radical prostatectomy. CONCLUSIONS PCDH17 methylation in serum is a frequent event in early-stage prostate cancer, and it is an independent predictor of BCR after radical prostatectomy.

Background Congenital heart disease (CHD) is one of the most prevalent birth defects. Housing renovations are a newly recognized source of indoor environmental pollution that is detrimental to health. A growing body of research suggests that maternal occupational exposure to renovation materials may be associated with an increased risk of giving birth to fetuses with CHD. However, the effect of indoor housing renovation exposure on CHD occurrence has not been reported. Methods A multi-hospital case–control study was designed to investigate the association between maternal periconceptional housing renovation exposure and the risk of CHD for offspring. In total, 346 cases and 408 controls were enrolled in this study from four hospitals in China. Exposure information was based on a questionnaire given to women during pregnancy. The association between housing renovation exposure and CHD occurrence was assessed by estimating odds ratios (OR) with logistic regression models adjusted for potential confounders. Results The risk for CHD in offspring was significantly associated with maternal exposure to housing renovations (AOR: 1.89, 95% CI: 1.29-2.77). There were similar risks for cardiac defects with or without extra-cardiac malformation (AOR of 2.65 and 1.76, respectively). Maternal housing renovation exposure may increase the fetus’ risk of suffering from conotruncal defect or anomalous venous return. There were significant risks for cardiac defects if the pregnant woman moved into a new house within one month after decoration at either 3 months before pregnancy (AOR: 2.38, 95% CI: 1.03 to 5.48) or during first trimester (AOR: 4.00, 95% CI: 1.62 to 9.86). Conclusions Maternal exposure to housing renovations may have an increased risk of giving birth to fetuses with some selected types of CHD. This relationship was stronger for women who moved into a newly decorated house. However, considering the limited number of subjects and the problem of multiple exposures, more research is needed to clarify the effects seen here.